Method and instrument for collecting fourier transform (FT) Raman spectra for imaging applications

Abstract

An instrument having an illumination source configured to illuminate a field of illumination on a surface of a substrate that is configured to hold a sample. The field of illumination typically has a diameter greater than 1 micron or an area greater than that of at least one pad of an array. The instrument also includes an interferometer, and a detectors. The instrument is configured to perform Fourier transform imaging without single spot scanning or without line scanning. Additionally, the instrument may include an illumination light source, an array detector and spectral processing electronics. A method of collecting Fourier transform (FT) data is also disclosed.

1. An instrument comprising:
 an illumination source configured to illuminate a field of illumination on a surface of a substrate that is configured to hold a sample, the field of illumination having a diameter greater than 1 microns, 
 a secondary lens configured to defocus light from the illumination source, 
 an interferometer, and 
 a detector, wherein the detector is an array detector comprising a plurality of detectors or a single detector having multiple channels, 
 further wherein the instrument is configured to perform Fourier transform imaging without single spot scanning or without line scanning. 
 
   
   
     2. The instrument of  claim 1 , wherein the sample emits electromagnetic radiation at one or more wavelengths different from an illumination wavelength of the illumination source. 
   
   
     3. The instrument of  claim 2 , wherein the sample emits electromagnetic radiation by Raman scattering. 
   
   
     4. The instrument of  claim 1 , wherein the interferometer is configured to create a varying phase shift in an electromagnetic spectrum and to create an interferogram. 
   
   
     5. The instrument of  claim 1 , wherein the detector is configured to detect an interferogram. 
   
   
     6. The instrument of  claim 5 , further comprising a microprocessor comprising software or a hardware to inverse Fourier transform the interferogram. 
   
   
     7. The instrument of  claim 1 , wherein the illumination source comprises a light source and a beam expander. 
   
   
     8. The instrument of  claim 1 , wherein the illumination source comprises multiple light sources emitting multiple beams. 
   
   
     9. The instrument of  claim 1 , wherein the illumination source comprises a single light source that is sufficiently spatially broad to expose an area on the surface of the substrate. 
   
   
     10. The instrument of  claim 1 , wherein the spectral bandwidth of the illumination source is narrower than 1 nm full-width at half-maximum. 
   
   
     11. The instrument of  claim 1 , wherein the interferometer comprises a beam splitter, a fixed mirror and a movable reference mirror. 
   
   
     12. The instrument of  claim 1 , further comprising a Bragg filter that substantially excludes JR signals and substantially passes Raman signals to the detector. 
   
   
     13. An instrument comprising:
 an illumination source configured to illuminate a field of illumination on a surface of a substrate that is configured to hold a sample, the sample comprising an array of pads, the field of illumination having an area greater than that of at least one pad of the array of pads, 
 a secondary lens configured to defocus light from the illumination source, 
 an interferometer; and 
 a detector, wherein the detector is an array detector comprising a plurality of detectors or a single detector having multiple channels, and 
 further wherein the instrument is configured to perform Fourier transform imaging without single spot scanning or without line scanning. 
 
   
   
     14. The instrument of  claim 13 , further comprising a Bragg filter that substantially excludes JR signals and substantially passes Raman signals to the detector. 
   
   
     15. The instrument of  claim 13 , wherein the interferometer comprises an electro- or thermo-optical material for providing an optical path difference. 
   
   
     16. The instrument of  claim 13 , wherein the Fourier transform imaging comprises Fourier transform imaging of a Raman signal. 
   
   
     17. The instrument of  claim 13 , wherein the Fourier transform imaging comprises Fourier transform imaging of a fluorescent signal. 
   
   
     18. The instrument of  claim 13 , wherein the sample comprise a biomolecule, a macromolecule, a nanomaterial, a capture molecule, Raman-active organic compound or a fluorescent compound. 
   
   
     19. The instrument of  claim 13 , further comprising a bandpass filter disposed along an optical path of an emitted electromagnetic radiation from the sample for removing electromagnetic radiation generated by the illumination source from being received at the detector. 
   
   
     20. The instrument of  claim 13 , wherein
 the illumination source is configured to illuminate a field of illumination and simultaneously expose multiple pads that emit electromagnetic radiation at one or more wavelengths different from an illumination Wavelength of the illumination source, 
 the interferometer is configured to create a varying phase shift in an electromagnetic spectrum and to create an interferogram from an original spectrum of the electromagnetic radiation emitted from the multiple pads and Fourier transform the original spectrum to a Fourier transformed spectrum, 
 the detector is configured to detect the interference patterns, and further comprising 
 a microprocessor comprising software or a hardware to inverse transform the Fourier transformed spectrum and reproduce the original spectrum, 
 wherein the instrument is configured to perform spatial imaging of the multiple pads without line scanning and without single spot scanning. 
 
   
   
     21. The instrument of  claim 20 , wherein detector converts the interferogram to an electrical signal. 
   
   
     22. The instrument of  claim 20 , wherein the electromagnetic radiation comprises light. 
   
   
     23. The instrument of  claim 20 , further comprising a beam emitter that emits a beam that strikes the multiple pads. 
   
   
     24. The instrument of  claim 23 , wherein the beam comprises laser. 
   
   
     25. The instrument of  claim 20 , further comprising optical elements to collect and concentrate the electromagnetic radiation emitted from the multiple pads. 
   
   
     26. The instrument of  claim 20 , wherein the detector is an array of single detectors. 
   
   
     27. The instrument of  claim 20 , wherein the detector is a charge coupled device. 
   
   
     28. The instrument of  claim 20 , wherein the electromagnetic radiation emitted from the multiple pads comprises a Raman signal, an infrared (IR) signal, a fluorescence signal, or a luminescence signal. 
   
   
     29. The instrument of  claim 20 , wherein the interferometer comprises two arms to pass a portion of electromagnetic radiation emitted from the multiple pads through each of the two arms. 
   
   
     30. The instrument of  claim 29 , wherein one of the two arms comprises a phase shifter. 
   
   
     31. The instrument of  claim 30 , wherein the phase shifter comprises a variable index material. 
   
   
     32. The instrument of  claim 20 , wherein the interferometer comprises a MEMS based device, an optical bench, a wafer having optical structures, an optical splitter or an optical waveguide. 
   
   
     33. The instrument of  claim 32 , wherein the optical splitter or the optical waveguide comprises optical fibers coupled to each other to form the optical splitter or the optical guide. 
   
   
     34. The instrument of  claim 32 , wherein the optical bench comprises a MEMS based moving arm. 
   
   
     35. A method of collecting Fourier transform (FT) data, comprising:
 illuminating a field of illumination in a plane containing a sample that emits an electromagnetic radiation, the field of illumination having a diameter greater than 1 microns, defocusing light from the illumination source with a secondary lens, 
 transforming the electromagnetic radiation emitted from the sample into an interferogram, 
 detecting an interferogram, and 
 transforming the interferogram into an emission spectrum by calculating Fourier transformation of the interfering patterns; 
 wherein FT data collection is performed without single spot scanning or without line scanning. 
 
   
   
     36. The method of  claim 35 , wherein the transforming the electromagnetic radiation emitted by the sample into an interferogram comprises creating the phase delay in the emission spectrum. 
   
   
     37. The method of  claim 35 , wherein the transforming the electromagnetic radiation emitted by the sample into an interferogram is performed by an interferometer. 
   
   
     38. The method of  claim 35 , wherein the detecting interferogram is performed by a detector and the transforming the interferogram into the emission spectrum is performed by a microprocessor. 
   
   
     39. The method of  claim 38 , wherein the detector is a charge coupled device. 
   
   
     40. The method of  claim 36 , wherein the interferometer comprises two arms to pass a portion of the electromagnetic radiation emitted from the sample through each of the two arms, further wherein one of the two arms comprises a phase shifter and the phase shifter comprises a variable index material. 
   
   
     41. The method of  claim 36 , wherein the interferometer comprises a MEMS based device, a wafer having optical structures, an optical splitter or an optical waveguide. 
   
   
     42. A method of collecting Fourier transform (FT) data, comprising:
 illuminating a field of illumination in a plane containing a sample comprising an array of pads that emit an electromagnetic radiation, the field of illumination having an area greater than that of at least one pad of the array of pads, 
 defocusing light from the illumination source with a secondary lens, 
 transforming the electromagnetic radiation emitted from the sample into an interferogram, 
 detecting the interferogram, and 
 transforming the inteferogram into an emission spectrum; and 
 wherein the FT data collection is performed without single spot scanning or without line scanning. 
 
   
   
     43. The method of  claim 42 , further comprising using a Bragg filter that substantially excludes JR signals and substantially passes Raman signals to the detector. 
   
   
     44. The method of  claim 42 , wherein the FT data comprises Raman data or fluorescence data. 
   
   
     45. A method of collecting Fourier Transform (FT) data with an optical imaging system, comprising:
 simultaneously exposing to an illumination source multiple pads that emit light at one or more wavelengths different from the illumination wavelength; 
 defocusing light from the illumination source with a secondary lens; 
 directing the emitted light from the multiple pads along a predetermined optical path; 
 interferometrically sampling the emitted light and scanning a spectral range that includes the one or more wavelengths of the light emitted from the multiple pads; 
 detecting with a detector the emitted light from the multiple pads simultaneously; and 
 collecting FT data corresponding to the detected light. 
 
   
   
     46. The method of  claim 45 , wherein the simultaneous exposing comprises expanding a beam emitted from a light source. 
   
   
     47. The method of  claim 45 , wherein the simultaneous exposing comprising generating light from multiple light sources. 
   
   
     48. The method of  claim 45 , wherein the simultaneous exposing comprises generating light from a single light source that is sufficiently spatially broad to expose said multiple pads simultaneously. 
   
   
     49. The method of  claim 45 , wherein the simultaneous exposing comprises generating a beam of light from a single light source and splitting the beam to provide multiple beams. 
   
   
     50. The method of  claim 45 , wherein the directing of the emitted light comprises collimating the emitted light. 
   
   
     51. The method of  claim 45 , wherein the directing of the emitted light along the optical path comprises reflecting the emitted light from the multiple pads along the optical path. 
   
   
     52. The method of  claim 45 , further comprising dichroically filtering the emitted light. 
   
   
     53. The method of  claim 45 , wherein interferometric sampling comprises directing a portion of the emitted light through an electro- or thermo-optical material for providing an optical path difference. 
   
   
     54. The method of  claim 45 , wherein the interferometric sampling comprises operating a Mach-Zehnder interferometer. 
   
   
     55. The method of  claim 54 , wherein the interferometric sampling comprises directing a portion of the emitted light through an electro- or thermo-optical material for providing an optical path difference. 
   
   
     56. The method of  claim 45 , wherein the FT data comprises Raman data or fluorescence data. 
   
   
     57. The method of  claim 45 , wherein the multiple pads comprise a biomolecule, a macromolecule, a nanomaterial, a capture molecule, Raman-active organic compound or a fluorescent compound. 
   
   
     58. The method of  claim 45 , further comprising removing light generated by the illumination source to prevent light generated by the illumination source from being received at the detector. 
   
   
     59. The method of  claim 45 , further comprising using a Bragg filter that substantially excludes JR signals emitted from the multiple pads and substantially passes Raman signals to the detector,
 wherein the multiple pads emit light at one or more wavelengths selected from the group consisting of IR, fluorescence, luminescence, and Raman. 
 
   
   
     60. The instrument of  claim 13 , wherein the interferometer comprises a Michelson interferometer wherein the Michelson interferometer comprises at least one movable mirror for adjusting an optical path difference. 
   
   
     61. The method of  claim 45 , wherein the interferometric sampling comprises operating a Michelson interferometer. 
   
   
     62. The method of  claim 61 , wherein the operating of the Michelson interferometer comprises adjusting at least one moveable mirror for adjusting an optical path difference.